10.1021/acsomega.8b01754.s001 Feng Cao Feng Cao Cari Orth Cari Orth Maureen J. Donlin Maureen J. Donlin Patrick Adegboyega Patrick Adegboyega Marvin J. Meyers Marvin J. Meyers Ryan P. Murelli Ryan P. Murelli Mohamed Elagawany Mohamed Elagawany Bahaa Elgendy Bahaa Elgendy John E. Tavis John E. Tavis Synthesis and Evaluation of Troponoids as a New Class of Antibiotics American Chemical Society 2018 CC 50 18 methicillin-resistant S Antibiotics Novel antibiotics MDR-A Acinetobacter baumannii anti-bacterial activity MIC 80 New Class MIC 80 values α- HT 92 troponoids Preliminary hits Escherichia coli reference strain tropolone novel troponoid antibiotics Staphylococcus aureus hepatoma cells MRSA Pseudomonas aeruginosa combat MDR 2018-11-08 18:37:45 Journal contribution https://acs.figshare.com/articles/journal_contribution/Synthesis_and_Evaluation_of_Troponoids_as_a_New_Class_of_Antibiotics/7316306 Novel antibiotics are urgently needed. The troponoids [tropones, tropolones, and α-hydroxytropolones (α-HT)] can have anti-bacterial activity. We synthesized or purchased 92 troponoids and evaluated their antibacterial activities against Staphylococcus aureus, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa. Preliminary hits were assessed for minimum inhibitory concentrations (MIC<sub>80</sub>) and cytotoxicity (CC<sub>50</sub>) against human hepatoma cells. Sixteen troponoids inhibited S. aureus/E. coli/A. baumannii growth by ≥80% growth at <30 μM with CC<sub>50</sub> values >50 μM. Two selected tropolones (<b>63</b> and <b>285</b>) inhibited 18 methicillin-resistant S. aureus (MRSA) strains with similar MIC<sub>80</sub> values as against a reference strain. Two selected thiotropolones (<b>284</b> and <b>363</b>) inhibited multidrug-resistant (MDR) E. coli with MIC<sub>80</sub> ≤30 μM. One α-HT (<b>261</b>) inhibited MDR-A. baumannii with MIC<sub>80</sub> ≤30 μM. This study opens new avenues for development of novel troponoid antibiotics to address the critical need to combat MDR bacterial infections.